The influence of thyroid hormone status on the regulation of hepatic carbohydrate metabolism by insulin, glucagon, catecholamines, vasopressin, and angiotensin will be investigated. Emphasis will be placed on defining the effects of both hypothyroidism and hyperthyroidism on the hormonal regulation of glycogenolysis in isolated rat liver parenchymal cells. The ability of the glycogenolytic hormones epinephrine, glucagon, vasopressin, and angiotensin and the ability of the anti-glycogenolytic hormone insulin to regulate glucose output, cyclic AMP levels, activation of protein kinase and the activation of glycogen phosphorylase will be measured in isolated hepatocytes from rats of altered thyroid states. We will define the component(s) responsible for an increased beta-adrenergic activation of phosphorylase and cyclic AMP accumulation in hepatocytes from the hypothyroid rats. The effects of altered thyroid status on the ability of insulin to regulate glycogen synthase activity will also be explored. The proposed project is designed to investigate the biochemical mechanisms involved in the modulation of hormonally-regulated hepatic carbohydrate metabolism by thyroid hormones.